Persistent Clinical Improvement Research Articles

Magnetic resonance imaging changes in spinal arteriovenous fistulae treated by endovascular means: are they reliable to predict complete cure of the fistula?

Regression or disappearance of MRI abnormalities is usually observed after treatment of spinal dural arteriovenous fistulae (sDAVF). To assess the correlation between spinal MRI (sMRI) changes with sDAVF exclusion and clinical outcome. Imaging data of patients treated with endovascular embolization for sDAVF between 2007 and 2023 were retrospectively analyzed. Spinal cord edema and perimedullary flow voids at baseline and 3-months' follow-up were compared between patients with and without sDAVF persistent occlusion and clinical improvement on the Aminoff and Logue Scale. Twenty-five patients were included in this study. At 3-months' follow-up, regression of spinal cord edema was significantly associated with sDAVF persistent occlusion (P=0.038). The combination of edema and flow voids regression was significantly associated with higher odds of a cured sDAVF (P<0.001) and clinical improvement (P<0.01). Improvement in the combination of the above-mentioned sMRI signs presented high sensitivity (100% (95% CI 78.20%-100%)) and negative predictive value (100% (95% CI 47.82%-100%)) for the detection of sDAVF cure compared with the criterion standard (digital subtraction angiography (DSA)). Patients with both spinal cord edema and flow voids regression at 3 months were more likely to present with a persistent occlusion of sDAVF and clinical improvement after endovascular embolization. Patients without sMRI improvement should be referred for DSA to seek recurrence of sDAVF.

7236 Long Term Extension of Osilodrostat Therapy in Canadian Patients with Cushing’s Disease Benefiting from the LINC 3 and LINC 4 Studies

Abstract Disclosure: L.M. Martel: Other; Self; LMD receives partial fellowship salary support though educational grants from Recordati Rare Disease Canada Inc and Pfizer Canada. G. Houde: Other; Self; GH served as a consultant for Novartis. C. Chik: Other; Self; grants and/or consulting fees from Pfizer, Ipsen, Novartis and Novo Nordisk Canada. S.A. Imran: Other; Self; consulting fees from Pfizer, Recordati and Novartis. E. Paron: Other; Self; employees of Recordati Rare Disease Canada Inc. F. Lebel: Other; Self; employees of Recordati Rare Disease Canada Inc. A. Lacroix: Other; Self; reports grants and personal consulting fees from Novartis, Recordati and Pfizer. Introduction: Osilodrostat, a potent oral 11β-hydroxylase inhibitor, provided rapid, sustained cortisol normalization in Cushing’s disease (CD) patients in two Phase III trials (LINC 3, NCT02180217; LINC 4, NCT02697734); persistent biochemical and clinical improvement of CD were reported after 72 and 96 weeks of therapy, respectively (10.1530/EJE-22-0317; 10.3389/fendo.2023.1236465). After study completion and continued clinical benefit with osilodrostat, patients could transition in a roll-over study (CLCI699C2X01B , NCT03606408). As osilodrostat is now approved for therapy of CS in Europe and CD in USA, but not in Canada, seven Canadian patients who had benefited from osilodrostat were transitioned to an investigator initiated study ((ISS-CA-2023, NCT06131580). Objective: To analyze the course of therapy with osilodrostat which allowed long-term biochemical and clinical control of CD since initiation of LINC 3 and LINC 4 core studies for up to 105 months. Methods: Retrospective review of clinical, biochemical and imaging data were collected through chart review of 11patients enrolled in four Canadian centers in LINC 3 and 4 in LINC 4 parent studies. Seven patients remained in the roll-over study until termination and initiation of the Canadian study on October 24 2023. Data from initiation of therapy until October 24 2023 were analyzed. Results: Of the eleven enrolled patients, four discontinued treatment due to muscle cramps, repeat transsphenoidal surgery (TSS) for corticotroph adenoma progression in 2 cases, and hyperandrogenism and opting for bilateral adrenalectomy in one case. Seven cases (5 LINC 3 and 2 LINC 4) pursued therapy in the extension study: 2 men and 5 women, mean age 46 y.o. (range 28-72). All but one had previous TSS, one Gamma Knife and 4 received previous medical therapy. The median 24 hour urinary free cortisol (UFC) before starting osilodrostat was 334 nnmol/d (2.4 x ULN; range 133-414). The median treatment duration was 82 months (range 67-105) and median time to normalize UFC was 36 days. The median maximal dose required to normalize UFC was 10 mg/day (4-60); dose was frequently reduced because of symptoms of relative cortisol withdrawal or adrenal insufficiency (n: 5) to 6.5 mg/day (range: 1 mg every 6 days to 30 mg/d) currently. Last median UFC was 60 nmol/d (range 22-154; 6/7 in normal range &amp;lt; 138nmol/d). Tumor growth occurred in 1 patient (2mm). All patients presented partial to complete improvement of CD features, whereas one patient developed moderate clinical hyperandrogenism, hypertension and borderline prolongation of QTc that normalized after a dose reduction. Conclusions: Osilodrostat can provide sustained biochemical and clinical control of hypercortisolism in patients with CD for up to 9 years; however drug efficacy and dose requirement varies greatly between patients and must be adjusted carefully and regularly during course of therapy. Presentation: 6/3/2024

Progressive encephalomyelitis with rigidity and myoclonus: a pediatric case report and literature review

BackgroundProgressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare and life-threatening autoimmune disease of the central nervous system. So far, only ten cases of PERM have been reported in children worldwide, including the one in this study.Case presentationWe report a case of an 11-year-old boy with PERM with an initial presentation of abdominal pain, skin itching, dysuria, urinary retention, truncal and limb rigidity, spasms of the trunk and limbs during sleep, deep and peripheral sensory disturbances, and dysphagia. A tissue-based assay using peripheral blood was positive, demonstrated by fluorescent staining of mouse cerebellar sections. He showed gradual and persistent clinical improvement after immunotherapy with intravenous immunoglobulin, steroids, plasmapheresis and rituximab.ConclusionsWe summarized the diagnosis and treatment of a patient with PERM and performed a literature review of pediatric PERM to raise awareness among pediatric neurologists. A better comprehension of this disease is required to improve its early diagnosis, treatment, and prognosis.

Optimization of treatment of morphea associated with metabolic syndrome

Objective. To study the efficacy of statins in the treatment of morphea in patients with metabolic syndrome and to study the dynamics of inflammatory markers on the background of atorvastatin use.Materials and methods. Atorvastatin at a dose of 20 mg per day was included in the treatment of patients with morphea asociated with metabolic syndrome. Clinical efficacy was evaluated after 3, 6, and 9–12 months on the basis of the dynamics of the modified localized scleroderma skin severity index mLoSSI, changes of laboratory markers of inflammation (C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha)), which was evaluated in 27 patients.Results. In patients whose treatment complex included atorvastatin, there was a persistent clinical improvement, which was manifested in a more pronounced decrease in the modified severity index of morphea mLoSSI relative to the control group after 6, 9-12 months of taking the drug, a marked decrease in the number of recurrences of the disease. When taking atorvastatin in patients with morphea with concomitant metabolic syndrome, there was a statistically significant decrease in the levels of inflammatory markers: CRP and TNF-alpha (p &lt; 0.05).Conclusion. The use of Atorvastatin at a dose of 20 mg per day in patients with limited scleroderma in combination with metabolic syndrome showed pronounced clinical efficacy, reduced the number of recurrences of the disease. There was a decrease in the levels of proinflammatory markers (CRP, TNF-alpha) when taking atorvastatin in patients with morphea associated with metabolic syndrome. The use of atorvastatin in patients with morphea and concomitant metabolic syndrome is effective in preventing relapses of morphea, reducing its severity.

Progressive Encephalomyelitis with Rigidity and Myoclonus with an Aggressive Presentation Mimicking Septic Shock: A Pediatric Case Report and Literature Review

AbstractProgressive encephalomyelitis with rigidity and myoclonus (PERM) is a relapsing–remitting neurological disorder that falls within the stiff person syndrome–spectrum disorders. We report a 16-year-old girl with PERM associated with an anti-glutamic acid decarboxylase (GAD) antibody. She had an aggressive initial presentation mimicking fulminant septic shock, followed by truncal and lower limb rigidity, stimulus-sensitive spasm, cognitive impairment, brainstem signs (hyperekplexia, nystagmus), and dysautonomia (urinary retention, constipation, facial flushing, blood pressure fluctuation). Cerebrospinal fluid, electroencephalography, and magnetic resonance imaging of the brain and spine showed features suggestive autoimmune encephalitis and myelitis. The serum anti-GAD antibody was positive, and the diagnosis of PERM was made. She had fluctuating clinical response despite intravenous immunoglobulin, steroids, plasmapheresis, and symptomatic medications. Eventually, in the fourth month since admission, she showed gradual and persistent clinical improvement after introducing rituximab. She was discharged after 6 months of hospitalization, and no relapse was observed in the first 3 years of follow-up.PERM is a rare and underrecognized condition in children. Contrary to previous reports, our case describes an aggressive and life-threatening presentation for PERM. Vague symptoms and the lack of gold diagnostic tests hinder a timely diagnosis. Our study also highlights the need for developing standardized diagnostic criteria and consensus in managing PERM.

Long-term treatment with fibrates and ursodeoxycholic acid in people with Primary Sclerosing Cholangitis is safe and associated with persistent clinical and biochemical improvement

Long-term treatment with fibrates and ursodeoxycholic acid in people with Primary Sclerosing Cholangitis is safe and associated with persistent clinical and biochemical improvement

Chronic encapsulated expanding hematomas after stereotactic radiosurgery for intracranial arteriovenous malformations.

Cerebral arteriovenous malformations (AVMs) are rare cerebral vascular lesions that are associated with high morbidity and mortality from hemorrhage; however, stereotactic radiosurgery (SRS) is a well-validated treatment modality. Few reports have delineated a subgroup of patients who develop delayed chronic encapsulated expanding hematomas (CEEHs) despite angiographic evidence of AVM obliteration following radiosurgery. In this report, the authors performed a retrospective review of more than 1000 radiosurgically treated intracranial AVM cases to delineate the incidence and management of this rare entity. Between 1988 and 2019, 1010 patients with intracranial AVM underwent Gamma Knife SRS at the University of Pittsburgh Medical Center. In addition to a review of a prospective institutional database, the authors performed a retrospective chart review of the departmental AVM database to specifically identify patients with CEEH. Pertinent clinical and radiological characteristics as well as patient outcomes were recorded and analyzed. Nine hundred fifty patients with intracranial AVM (94%) had sufficient clinical follow-up for analysis. Of these, 6 patients with CEEH underwent delayed resection (incidence rate of 0.0045 event per person-year). These patients included 4 males and 2 females with a mean age of 45.3 ± 13.8 years at the time of initial SRS. Four patients had smaller AVM volumes (4.9-10 cm3), and 3 of them were treated with a single SRS procedure. Two patients had larger-volume AVMs (55 and 56 cm3), and both underwent multimodal management that included staged SRS and embolization. Time to initial recognition of the CEEH after initial SRS ranged between 66 and 243 months. The time between CEEH recognition and resection ranged from 2 to 9 months. Resection was required because of progressive neurological symptoms that correlated with imaging evidence of gradual hematoma expansion. All 6 patients had angiographically confirmed obliteration of their AVM. Pathology revealed a mixed chronicity hematoma with areas of fibrosed blood vessels and rare areas of neovascularization with immature blood vessels but no evidence of a persistent AVM. All 6 patients reported persistent clinical improvement after hematoma resection. CEEH after SRS for AVM is a rare complication with an incidence rate of 0.0045 event per person-year over the authors' 30-year experience. When clinical symptoms progress and imaging reveals progressive enlargement over time, complete resection of a CEEH results in significant clinical recovery. Knowledge of this rare entity facilitates timely detection and eventual surgical intervention to achieve optimal outcomes.

A prospective study of direct-acting antiviral effectiveness and relapse risk in HCV cryoglobulinemic vasculitis by the Italian PITER cohort.

Background and AimsMixed cryoglobulinemia is the most common HCV extrahepatic manifestation. We aimed to prospectively evaluate the cryoglobulinemic vasculitis (CV) clinical profile after a sustained virologic response (SVR) over a medium‐term to long‐term period.Approach and ResultsDirect‐acting antiviral–treated cryoglobulinemic patients, consecutively enrolled in the multicentric Italian Platform for the Study of Viral Hepatitis Therapy cohort, were prospectively evaluated. Cumulative incidence Kaplan‐Meier curves were reported for response, clinical deterioration, relapse and relapse‐free survival rates. Cox regression analysis evaluated factors associated with different outcomes. A clinical response was reported in at least one follow‐up point for 373 of 423 (88%) patients with CV who achieved SVR. Clinical response increased over time with a 76% improvement rate at month 12 after the end of treatment. A full complete response (FCR) was reached by 164 (38.8%) patients in at least one follow‐up point. CV clinical response fluctuated, with some deterioration of the initial response in 49.6% of patients (median time of deterioration, 19 months). In patients who achieved FCR and had an available follow‐up (137 patients) a relapse was observed in 13% and it was transient in 66.7% of patients. The rate of patients without any deterioration was 58% and 41% at 12 and 24 months, respectively. After achieving SVR, a clinical nonresponse was associated with older age and renal involvement; a clinical deterioration/relapse was associated with high pretreatment rheumatoid factor values, and FCR was inversely associated with age, neuropathy, and high cryocrit levels.ConclusionIn patients with CV, HCV eradication may not correspond to a persistent clinical improvement, and clinical response may fluctuate. This implies an attentive approach to post‐SVR evaluation through prognostic factors and tailored treatment.

PASCAL-based mitral valve repair in an all-comer population: acute and mid-term clinical results.

AimsWe investigated short and mid‐term safety and efficacy of the PASCAL system for percutaneous mitral valve repair (PMVr) in severe mitral regurgitation (MR) in an all‐comer population.Methods and resultsIn the first consecutive 41 patients undergoing PMVr using the PASCAL system in our centre, procedural success and safety were assessed. Efficacy in improving MR and functional class were evaluated. Median patient age was 74 years, 58.5% were male patients, and median European System for Cardiac Operative Risk Evaluation Score II was 5.1%. All patients suffered from severe MR with 59% functional MR, 29% degenerative MR, and 12% of mixed aetiology MR. The technical success rate was 90%, limited by four cases where PASCAL implantation was aborted due to a prohibitive mitral gradient. On average, 1.16 PASCAL devices per patient were implanted. All patients successfully implanted with a PASCAL device were discharged with MR grade ≤ 2 and 79% with MR grade ≤ 1. Mean follow‐up was 8.7 ± 4.9 months. Ninety‐seven per cent of patients remained at MR ≤ 2 at follow‐up, which translated into a significantly improved New York Heart Association functional class as well as a significant reduction of systolic pulmonary artery pressure and brain natriuretic peptide levels. The procedure‐related rate for major adverse events was 3%. Neither early nor late single‐leaflet detachment was found. In one patient, air embolism occurred, resulting in modification of the PASCAL instructions for use.ConclusionsPercutaneous mitral valve repair using PASCAL in a real‐world, all‐comer population was feasible and safe, resulting in a significant mid‐term reduction of MR with persistent clinical improvement.

Heparin-Bonded Stent-Graft for the Treatment of TASC II C and D Femoropopliteal Lesions: 36-Month Results of the Viabahn 25 cm Trial

Purpose: To evaluate the 36-month technical and clinical outcome after implantation of the 25-cm Viabahn endoprosthesis with Propaten bioactive surface in TransAtlantic Inter-Society Consensus II C and D lesions of the superficial femoral and proximal popliteal arteries. Materials and Methods: This prospective, multicenter, single-arm trial (ClinicalTrials.gov; identifier NCT01263665) enrolled 71 patients (mean age 66.7±8.3 years; 50 men) with lifestyle-limiting claudication or rest pain (Rutherford category 2–4) and long (>20-cm) lesions of the superficial femoral and proximal popliteal arteries. Primary endpoint was primary patency at 36 months. Secondary endpoints included primary assisted patency; secondary patency; freedom from target lesion revascularization (TLR); freedom from a composite of death, target vessel revascularization (TVR), and amputation; clinical success; and freedom from device fracture. Results: Primary patency estimated by Kaplan-Meier analysis was 40.6% at 36 months. Primary assisted patency and secondary patency estimates were 53.0% and 96.9%, respectively. Within 36 months, 27 patients had to undergo a TLR. Twenty-five patients (35.2%) had a TVR. Freedom from the composite of death, TVR, and amputation endpoint was 44.5%. The estimate of the sustained clinical success with stable or improved Rutherford category was 58.5%. No stent fracture was detected during follow-up. Conclusion: The primary patency rate without reintervention after treatment of long femoropopliteal lesions is low. However, secondary patency after implantation of a Viabahn endoprosthesis is high and seems to be superior to the use of other revascularization techniques, resulting in persistent clinical improvement.

Clinical Efficacy of Routinely Administered Belimumab on Proteinuria and Neuropsychiatric Lupus.

Background and Objectives: Belimumab (BEL) is a monoclonal antibody approved for the treatment of active systemic lupus erythematosus (SLE) but not for lupus nephritis (LN) and neuropsychiatric systemic lupus erythematosus (NPSLE). We aimed to assess BEL's effects on these severe, potentially life-threatening manifestations.Methods: Retrospective observational cohort study using routine clinical data in a case series of patients with SLE receiving BEL.Results: Sixteen patients received BEL therapy for active SLE. Nine were excluded because they had no LN or NPSLE. Six suffered from LN, and one patient had NPSLE. All LN patients received BEL in addition to standard therapy including glucocorticoids, hydroxychloroquine, and mycophenolate mofetil in five cases, and tacrolimus in one case. Three patients with proteinuria >1,000 mg/g creatinine responded well (one complete, two partial renal responses); all other patients had decreasing proteinuria and a reduction in anti-dsDNA levels. The patient with NPSLE who had failed previous therapies had persistent clinical improvement of cutaneous and neuropsychiatric manifestations. There was one mild allergic reaction and one lower respiratory tract infection, but no other adverse events. One patient discontinued therapy due to a lack of improvement in clinical symptoms, another because of clinical remission.Conclusions: In our series, BEL led to a decrease of proteinuria in patients with proteinuria of more than 1,000 mg/g creatinine despite standard of care treatment, and led to a marked clinical improvement in one patient with NPSLE. No adverse events were observed. Routinely administered BEL shows clinical efficacy on non-approved manifestations, but careful patient selection is warranted.

Ixekizumab Results in Persistent Clinical Improvement in Moderate-to-Severe Genital Psoriasis During a 52 Week, Randomized, Placebo-Controlled, Phase 3 Clinical Trial

Ixekizumab was efficacious in treating moderate-tosevere genital psoriasis over 12 weeks. We evaluated the long-term efficacy and safety of ixekizumab for up to 52 weeks. Patients were randomized to 80 mg ixekizumab every 2 weeks or to placebo through Week 12, then received 80 mg open-label ixekizumab every 4 weeks through Week 52. In patients initially randomized to ixekizumab, clear or almost clear genital skin was achieved for 73% of patients at Week 12 and 75% at Week 52. Persistent improvements were also observed for overall psoriasis, genital itch, and the impact of genital psoriasis on the frequency of sexual activity. The safety profile was consistent with studies of ixekizumab in patients with moderate-to-severe plaque psoriasis. Ixekizumab provided rapid and persistent improvements in the signs and symptoms of genital psoriasis for up to 52 weeks of treatment.

Persistent clinical improvement in genital psoriasis through one year of treatment with ixekizumab: Results of a randomized, placebo-controlled phase 3 clinical trial in patients with moderate-to-severe genital psoriasis (IXORA-Q)

Persistent clinical improvement in genital psoriasis through one year of treatment with ixekizumab: Results of a randomized, placebo-controlled phase 3 clinical trial in patients with moderate-to-severe genital psoriasis (IXORA-Q)

Neurotransmitter trafficking defect in a patient with clathrin (CLTC) variation presenting with intellectual disability and early-onset parkinsonism

IntroductionClathrins play a key role in endocytosis, recycling, and trafficking as well as the generation of presynaptic vesicles. We report a new clinical condition associated with a de novo variant in the CLTC gene, which encodes the clathrin heavy polypeptide. Case reportThis 30-year-old woman presented with a developmental disorder during childhood that progressed to mild cognitive decline in late childhood and relapsing-remitting hypokinetic-rigid syndrome with severe achalasia, weight loss, and mood disorder in adulthood. 123I-Ioflupane SPECT was normal. Blood phenylalanine was slightly increased and PAH sequencing revealed compound heterozygosity for two variants, p.[Asp151Glu]:[Thr380Met]. CSF examination unexpectedly detected a remarkable reduction of homovanillic, 5-hydroxyindolacetic, and 5-methylthetrahydrofolic acids, which could not be ascribed to any alteration of tetrahydrobiopterin and related biogenic amine pathways. MethodsTrio-based exome sequencing was performed. ResultA de novo missense variant (c.2669C > T/p.Pro890Leu) was detected in CLTC. Treatment with biogenic amine precursors was ineffective, while the inhibitor of MAO-A selegiline resulted in persistent clinical improvement. ConclusionsWe suggest CLTC defect as a new disorder of biogenic amine trafficking, resulting in neurodevelopmental derangement and movement disorder. Neurotransmitter depletion in CSF may be a biomarker of this disease, and selegiline a possible treatment option.

192 Multi-Watt Near Infrared Phototherapy is an Effective Treatment for Depression

AbstractBackgroundDepression treatment is hampered by low efficacy of antidepressant medications and concerns about alternative modalities. Animal studies of treatment with low-level (0.5 Watt or less) near infrared (NIR) light from diodes has shown some benefit in models of traumatic brain injury (TBI) with evidence of reduced lesion size, increased neurotrophin production, synaptogenesis, fewer apoptotic cells, and improved neurological function. Two small case series have demonstrated transient clinical improvement with low-level NIR treatment given on a daily basis over several weeks. We have previously shown marked and persistent clinical improvement in a case series of patients with chronic mild-to-moderate (m-MTBI) after treatmentwith NIR at a power of 9 Watts or greater. We also have published a review of the potential for application of NIR for the treatment of depression. The current study explores NIR efficacy in a proof-of-concept study as a treatment for depression.MethodsThirty-nine sequential patients treated for TBI between March 2013 and May 2017 provided depression self-assessment data and/or were administered the Hamilton Depression Rating Scale. Each completed the Quick Inventory of Depression Symptomatology-Self Reports (QIDS) before and after treatment. Patients received transcranial multi-Watt near-infrared light treatment (NILT) using near-infrared lasers (810/980 nm at 8-15 Watts) applied to forehead and temporal regions bilaterally for 9-12 minutes to each area.ResultsFor 36 of the 39 patients, after 16.82 + 6.26 treatments, QIDS scores indicated a robust response (decrease of QIDS total score by &gt; 50%). For 32 of 39 patients post-treatment QIDS scores indicated a remission from depression (decrease of QIDS total score &lt; 5). Overall, the QIDS score fell from 14.10 + 3.39 to 3.44 + 3.39 SD (p=6.29 X 10-19). With 12 or fewer treatments, QIDS score dropped from 14.83 + 2.55 to 4.17 + 3.93. Patients receiving 13 or more treatments showed a change in QIDS score from 13.67 + 3.64 to 3.11 + 3.14. Those (N=15) who received the entire treatment course within 8 weeks or less (5.33 + 1.72 weeks) showed a change in QIDS score from 13.86 + 3.14 to 4.5 + 3.94. Suicidal ideation resolved in all, but two patients. The non-responsive patients are described in detail. Patients remained in remission for up to 55 months after a single course of treatment.ConclusionThis is the first report of high-powered NILT showing efficacy for depression. Patients saw benefit often within 4 treatments and some had resolution of depressive symptoms in as little as 4 weeks. These data raise an intriguing possibility – that NILT may be a safe, effective, and rapid treatment for depression. A double-blind, placebo controlled trial is warranted to verify these proof-of-concept data.Funding AcknowledgementsNeuro-Laser Foundation

Improvement in Venous Clinical Severity Score Following Ultrasound Guided Foam Sclerotherapy

Background: Ultrasound guided foam Sclerotherapy (UGFS) is a simple and cost effective procedure in the management of lower limb varicose vein with very few studies on Indian population. This study is focused on clinical improvement evaluated by venous clinical severity score (VCSS) at 2 months following UGFS, in a rural population in South Kerala. Objective: To assess improvement in Venous Clinical Severity Scoring (VCSS), two months following UGFS in lower limb varicose veins. Methods: A prospective, observational study of 58 cases was done between December 2015 and November 2016, in a rural population in Kerala. 58 patients underwent UGFS during the study and their pre UGFS VCSS score was documented. Of these, 49 patients came back for follow up at 2 months, for post UGFS VCSS and Duplex Doppler evaluation to assess the effectiveness of UGFS. Results: Pre procedure VCSS score of 49 patients, ranged between 3.0-19.0 (Mean=10.7) and post procedure VCSS were between 2-16 (Mean=7.6), which is statistically significant (P=0.01). Decrease in VCSS score by about 3-5 was noted in 44 out of the 49 patients who had successful outcome with no persistent reflux and clinical improvement was also seen in 5 patients with persistent reflux. Of the 19 patients with venous ulcer, there was healing of ulcer at 2 month post UGFS review. Conclusion: UGFS is a simple, cost effective procedure which leads to significant improvement in clinical symptoms and decreasing morbidity associated with chronic venous disease.

Long-term Clinical and Radiological Outcome Evaluation of 3- and 4 Level ACDF with a Zero-profile Implant. Impact of Cervical Sagittal Alignment on Clinical Outcome

Introduction Concerns remains on the role of ACDF in multilevel cervical disease as opposite to posterior approaches, and on the importance of cervical sagittal alignment in influencing long-term clinical outcome. We aim to analyze the efficacy of 3- and 4-level ACDF with a zero-profile implant in restoring cervical sagittal alignemnt as well as the impact of alignment on clinical outcome, both at early and long-term follow-up. And also to evaluate type and rate of complications. Material and Methods 24 patients (14 male), ranging in age from 41 to 77 years (mean 58.4) and suffering from multilevel spondylosis, were enrolled. Neurological improvement was graded according to the Nurick scale. NDI, VAS and SF-36 were used for pre- and postoperative functional evaluation. Imaging included X-rays, CT and MRI before surgery; X-rays were obtained at every follow-up visit and CT scan at last follow-up. Sagittal alignment was assessed before and after surgery using the Cobb method. Fusion rate was studied on both X-rays and CT scan. Complications were analyzed and dysphagia evaluated using the Bazaz scale. Results Mean follow-up ranges from 24 to 72 months (mean 39). No intra- or postoperative complications, either related to surgical technique or to devices implanted, were encountered. Mean neck pain VAS score decreased from a 6.7 ± 2.9 to 1.6 ± 2.3 ( p &lt; 0.01). Mean arm pain VAS score decreased from 5.9 ± 2.9 to 0.9 ± 1.4 ( p &lt; 0.01). There were significant improvements ( p &lt; 0.01) in SF36 and NDI following surgery. Five patients complained of mild dysphagia (20.8%). Three of them (12.5%) showed complete resolution within two months (short-term dysphagia); the other two (8.3%) within six months (medium-term dysphagia). No case of long-term dysphagia (more than 6 months) was observed. According to Pitzen criteria, radiographic fusion was achieved in 90% of patients. Cobb angle had a significant improvement both after surgery and at long-term follow-up. Conclusion 3- and 4-level ACDF with a zero-profile device is safe and effective. It allows satisfactory neurological and functional outcome as well as interbody fusion. Multilevel anterior approach provides satisfactory sagittal alignment restoration, and this is associated with persistent clinical improvement at long-term follow-up.

Arthroscopic treatment of femoroacetabular impingement shows persistent clinical improvement in the mid-term.

The concept of femoroacetabular impingement (FAI) and the indication for surgical intervention have been established in the last decade. Despite promising short-term results and emerging arthroscopic techniques, it remains unclear whether patients benefit from surgical correction in the mid- to long-term and whether progressive joint degeneration can be prevented. A retrospective study of our first 50 consecutive patients who underwent arthroscopic correction for FAI was conducted. The modified Harris hip score (mHHS) was assessed preoperatively and at final follow-up. In addition, the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) and a subjective hip value (SHV) were added at final follow-up. Degenerative changes according to Kellgren and Lawrence scale and the α angle were analyzed preoperatively and on the most recent radiograph. Of a total of 50 patients, 44 (24 male, 20 female) with a mean age of 34.3years (17-65) were available with complete follow-up. Of these 44 patients, 39 were treated with correction of the femoral offset for isolated cam deformity, 5 with additional focal pincer correction and partial labral resection. After a mean follow-up of 66.3±14.5months the mHHS had improved significantly from 67.2±6.4 preoperatively to 86.4±13.5 (p<0.001). The WOMAC score (converted to 0=best/100=worst) resulted in mean indices for the subcategories pain, stiffness and function of 11.8±16.5, 12.2±17.8 and 9.1±16.1. The SHV was reported with a mean of 77.7±21.8% at final follow-up. The α angle was reduced significantly from 57.2°±10.1° to 46.3°±7.4° (p<0.001). The Kellgren and Lawrence score showed a non-significant trend from 2.0±0.8 preoperatively to 2.2±0.9 in the most recent radiograph (p=0.46). 5 patients had been converted to a total hip arthroplasty a mean of 28±7.1months postoperatively. These patients were significantly (p<0.01) older with a mean age of 49.8±7.8years and showed significantly higher present osteoarthritic changes with an average Kellgren and Lawrence score of 2.6±2.5 before FAI correction (p<0.01). Arthroscopic correction of femoroacetabular impingement results in a persistent clinical improvement without significant progression of degenerative changes in the majority of patients. The indication for surgery should be established cautiously when degenerative changes are present. Level IV, Case series with no comparison group.

Pulmonary Artery Branch Stent Implantation in Congenital Heart Disease: A 10-Year Multicenter Experience

Background: Stent implant is considered the treatment of choice for most cases of congenital or postoperative pulmonary artery branch stenosis in patients with congenital heart defects. However, there are still doubts on the clinical effectiveness and the incidence of complications of this technique that need to be elucidated.Methods: This multicenter study has a descriptive, observational and retrospective design. The procedures were performed between January 2005 and April 2015. Twenty-five patients with pulmonary artery branch stenosis underwent stent implant and were followed-up both clinically and by different imaging tests. Persistent clinical and/or anatomic improvement defined clinical effectiveness.Results: Average age was 9.48 years (2 months-34 years), mean weight was 27.54 kg (3-104 kg) and 44% were women. The most frequent congenital heart defects in the treated cohort were tetralogy of Fallot and its variants, followed by single ventricle heart physiology after bidirectional Glenn shunt and/or Fontan-Kreutzer procedures. Right ventricular systolic and pulmonary artery pressure decreased significantly after the intervention (from 68.35 mmHg to 45.8 mmHg and from 47.4 mm Hg to 32 mm Hg, respectively) (p < 0.0001). The initial minimum diameter of the treated pulmonary artery branch increased significantly after the procedure (from 3.98 mm to 9.82 mm, p < 0.0001). The incidence of complications was 8% (n = 2) and the clinical effectiveness of the procedure was good in 22 patients (88%).Conclusions: Stent implant in pulmonary artery branch stenosis is a safe and feasible though challenging technique, with significant clinical and anatomic improvement. The procedure represents an alternative to surgery and decreases the need for reinterventions in patients with congenital heart defects.

Neuropsychiatric phenotype in a child with pseudohypoparathyroidism

Pseudohypoparathyroidism (PHP) is a rare heterogeneous genetic disease characterized by end-organ resistance to parathyroid hormone. In adulthood, heterogeneous neurological and psychiatric disorders have been reported which are associated with hypoparathyroidism in general and with PHP in particular, while for childhood, data are scanty. We report a case of a boy with PHP type 1b, in whom neurological signs at the onset prevailed, characterized by tic-like dyskinesias associated with a series of heterogeneous not well-defined neurological and behavioral features, describing the diagnostic work-up performed and the follow-up. We suggest that the diagnostic hypothesis of PHP might be considered when dealing with a child with tic-like dyskinesias, especially if associated with a series of heterogeneous not well-defined neurological and behavioral features. In these cases, treatment with calcitriol and calcium has to be started as soon as possible to achieve a prompt and persistent clinical improvement.